In this study, we investigated the distribution patterns of brain atrophy in patients with alcohol addiction using VBM, which allows the analysis of regional GM and WM partitions without predefining regions of interest. This method provides the possibility to analyse complex patterns of brain atrophy also in those brain regions that are difficult to investigate using anatomically based methods of volumetry. Previous studies have shown that VBM is more sensitive in detecting subtle changes in brain volume than conventional methods of volumetry.14,16,20
To minimise methodological bias, we used an optimised protocol based on the creation of study‐specific templates and the modulation of the segmented GM partitions to compensate for volume changes in brain normalisation.20
One of the most intriguing findings of this study is the pronounced decrease in GM volumes in the thalamus of patients with alcohol addiction. These data are consistent with several previous reports on the involvement of thalamic neuronal circuits in different behavioural changes in patients with alcohol dependence.8
On the other hand, our data contradict those of a previous study demonstrating reduced thalamic volume only in subjects with Korsakoff's syndrome but not in subjects with chronic alcoholism using conventional MRI volumetry.4
In contrast with that, George et al21
have shown that patients with alcohol addiction, when exposed to alcohol cues, have increased brain activity in the prefrontal cortex and anterior thalamic regions, which are associated with regulation of emotions, attention and appetitive behaviour. The most recent study on this issue has shown a significant role of the thalamus in processing cue‐related information and in controlling alcohol‐related behaviour.22
The reduction of GM volumes found in this study may suggest functional insufficiency of thalamic regions that are responsible for altered behavioural patterns occurring in patients with alcohol addiction.
The analysis of our data suggests alcohol‐induced alterations of the posterior hippocampus as well. Although previous neuropathological studies failed to prove alcohol‐associated neurodegeneration of the hippocampus in human brains,11
animal models have demonstrated that binge drinking of ethanol can produce necrotic neurodegeneration in the areas of the brain most closely associated with the hippocampus.23
Our findings support the hypothesis of involvement of the hippocampus in the brain of patients with alcohol addiction. There exists ample evidence of possible mechanisms underlying the effect of alcohol on the hippocampus. The hippocampus is the area with the greatest increase in lipofuscin deposition in neurons as a result of chronic alcohol consumption.24
Further, the fatty acid ethyl esters produced in the brain from ethanol are known to be particularly damaging to the hippocampus.25
Our data are further consistent with the previous findings on involvement of frontal cortical areas in the brain of patients with alcohol addiction. Numerous neuropsychological studies demonstrated substantial deficits in frontal executive functions in patients with alcohol dependence.6,26,27
Our results suggest substantial volume reduction in the middle frontal gyrus and precentral gyrus, although no changes were detected in other frontal regions. These findings support previous reports on decreased glucose metabolic rates in middle frontal regions in patients with alcohol addiction 28
and a reduction of γ aminobutyric acid A/benzodiazepine receptors in superior medial parts of the frontal lobes.29
A significant decrease in WM volumes in the pons and cerebellum in the our study is consistent with the previous results that have shown the alcohol‐associated degeneration of pontine and cerebellar WM in patients with alcohol addiction,7,30,31
whereas in healthy subjects these regions have been shown to remain stable across the entire age span in both men and women.32
The significant decrease in periventricular WM found in our study is also consistent with previous data; however, the analysis and interpretation of these changes in VBM studies is difficult because of the possible bias due to partial volume effects.
Even low‐to‐moderate consumption of alcohol was associated with brain atrophy in a study of middle‐aged men.5
Ethanol can increase the release of arachidonic acid from cell membranes and cause oxidative stress in the brain by increased cyclo‐oxygenase activity. Furthermore, hydroxyethyl free radicals derived directly from ethanol are nearly as damaging as hydroxyl radicals.33
There is also evidence from animal studies that alcohol causes cell death. Rats fed a liquid diet containing moderate amounts of ethanol for 6 weeks had a 66.3% decrease in the number of new neurons and a 227–279% increase in cell death in the dentate gyrus as compared with rats fed an alcohol‐free diet.34
In general, our data support the previous assumption that the regional reduction of GM volumes may result from alcohol‐induced neuronal loss, whereas global brain shrinkage might be caused by loss of WM.1
Furthermore, our results support previous findings on alteration of selected regions of the frontal cortex and cerebellum in patients with alcohol addiction and suggest the involvement of the anterior thalamus, posterior hippocampus, insular cortex and periventricular WM in alcohol‐associated brain damage. A causal relationship between alcohol consumption and regional brain atrophy still demands further research, whereas VBM seems to represent a tool of choice for in vivo detection of the brain areas predisposed to alcohol‐induced damage.